In primary colorectal tumors, driver mutations in genes such as adenomatous polyposis coli (APC), tumor protein p53 (TP53), Kirsten rat sarcoma viral oncogene homolog (KRAS), and SMAD family member 4 (SMAD4) are associated with multistep tumorigenesis through the adenoma–carcinoma sequence [30,35,36,37]. This evidence concerns the gene SMAD4 and adenoma.